Antiradical, antimicrobial and enzyme inhibition evaluation of sulfonamide derived esters; synthesis, X-Ray analysis and DFT studies Muhammad Danish a, * , Ayesha Bibi a , Khola Gilani a , Muhammad Asam Raza a , Muhammad Ashfaq a , Muhammad Nadeem Arshad b , Abdullah Mohamed Asiri b, ** , Khurshid Ayub c a Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan b Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia c Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad, KPK 22060, Pakistan article info Article history: Received 1 June 2018 Received in revised form 29 July 2018 Accepted 31 July 2018 Available online 3 August 2018 Keywords: Antioxidant DFT Enzyme inhibition Ester Sulfonamide abstract Two carboxylate esters (methyl: (I) and ethyl: (II)) of 4-{(4-methylphenylsulfonamido)- methyl}cyclo- hexanecarboxylic acid (sulfonamide) were synthesized and characterized by FTIR and X-ray crystallog- raphy. DFT studies were conducted in order to optimize the structures using Gaussian software which confirmed the bond angels and bond lengths obtained from single crystal analysis. Both Compounds (I and II) were evaluated for their biological studies viz; antioxidant activity (DPPH), enzyme inhibition activity (esterase and proteases), antibacterial (Halomonas halophila, Halomonas salina, Shigella sonnei, Bacillus subtilis, Chromohalobacter salexigens, Chromohalobacter israelensis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae) and anti-fungal (Aspergillus niger and Alternaria alternata). Results depicted that II is more active as compared to I in antioxidant and esterases while I is more potent against protease while moderate results were shown by both. © 2018 Published by Elsevier B.V. 1. Introduction Sulfonamides have been found to show broad pharmacological profile. They are stable in human body and being used for the treatment of various diseases i.e. tumor, diabetes and other major pathogens. Moreover, they are used in agriculture field as well as insecticides and herbicides. They are less toxic as compared to other drugs and are scalable [1e3]. It has been reported that minor variation in the structure of sulfonamide gives vast range of ap- plications both qualitatively as well as quantitatively. Sulfonamides have been proved to be wonderful drugs as they serve the hu- manity meritoriously for health e.g. as antitumor, antibacterial, antifungal and inhibition against lipoxygenase enzyme [4e7]. As b3 adrenergic agonist, they serve for the treatment of obesity and type 2 diabetes [8e10]. The biological potential of the sulfonamides depends to which way, they attach to their respective receptor or enzyme. This aptitude of binding depends upon proton-ligand complex of the sulfonamides [11]. After the discovery of sulfanil- amide, so many chemical alteration have been done and evaluated their therapeutic results. Up-to date greater than 20,000 sulfanil- amide derivatives have been synthesized following different syn- thetic schemes. These syntheses have resulted in the finding of new agents with changeable pharmacological properties [12]. Density functional theory (DFT) has long been renowned as a best tool in the understanding of organic complex previous methods used in the past. Detailed analyses on the performance of various DFT methods have been carried out predominantly for the optimized geometry or structure [13]. Keeping in view such therapeutic ap- plications, new esters derived from sulfonamides were synthesized and characterized. Evaluation of these synthesized compounds for their pharmacological profile involving enzyme inhibition, bacte- ricidal, fungicidal and anti-oxidant potential is also part of this research task. 2. Experimental Chemical for this research task were purchased from Alfa Aesar and Merck (UK). Solvents used; Methanol, Ethanol and Dimethyl Sulfoxide of analytical grade were purchased from Merck (UK). * Corresponding author. ** Corresponding author. E-mail addresses: drdanish62@gmail.com (M. Danish), aasiri2@kau.edu.sa (A.M. Asiri). Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: http://www.elsevier.com/locate/molstruc https://doi.org/10.1016/j.molstruc.2018.07.116 0022-2860/© 2018 Published by Elsevier B.V. Journal of Molecular Structure 1175 (2019) 379e388